• Journal of Korean Neurosurgical Society
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• v.59 no.2
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• pp.98-105
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• 2016

Objective : Lumbar disc herniation can induce sciatica by mechanical compression and/or chemical irritation. The aim of this study was to compare the effects of GCSB-5 (Shinbaro$^{(R)}$) and NSAIDs on pain-related behavior and on the expressions of microglia, astrocytes, CGRP, TRPV1, IL-6, and CX3CL1 in a rat model of lumbar disc herniation. Methods : 112 male Sprague-Dawley rats underwent implantation of nucleus pulposus to a dorsal root ganglion (DRG). Rats were divided into five groups as follows; a saline group (the vehicle control group) (n=27), a 10 mg/kg aceclofenac group (the aceclofenac group) (n=22), and 100, 300 or 600 mg/kg GCSB-5 groups (the GCSB-5 100, 300, or 600 groups) (n=21 for each group). Rats were tested for mechanical allodynia at 3 days after surgery and at 1 day, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after treatment commencement. Immunohistochemical staining of microglia (Iba1), astrocytes (GFAP), CGRP, and TRPV1, and PCR for IL-6 and CX3CL1 were performed on spinal dorsal horns and DRGs at 56 days after medication commencement. Results : After 56 days of GCSB-5 300 administration, mechanical withdrawal thresholds were significantly increased (p<0.05), and immunohistochemical expressions of Iba1, GFAP, CGRP, and TRPV1 were reduced than other groups, but this difference was not statistically significant. Conclusion : These results indicate GCSB-5 reduces mechanical allodynia and downregulates neuroglial activity and the expressions of CGRP and TRPV1 in the spinal segments of a rat model of lumbar disc herniation.

• Journal of Nutrition and Health
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• v.24 no.2
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• pp.114-123
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• 1991

This study was designed to investigate the effects of aerobic dancing and/or Ca supplemen-tation for six months on Ca metabolism in postmenopausal women. The subjects were healthy 29 women aged from 60 to 70 years old. They were divided into four groups ; placebo and Ca supplementation group with and without exercise. The amount of Ca supplemented was 500mg a day. The frequency of doing exercise was three times a week and it took 40 minutes to complete once all the course of aerobic dancing programmed for old women. The results were summarized as follows : 1) Bone density of the second lumbar spine and ward's triangle measured after experiment decreased significantly in control group as compared with pre-experimental level(P<0.05). On the contrary it showed a tendency to increase or maintained the pre-experimental level after experiment in other groups. 2) Urinary Ca/creatinine and P/creatinine ratios did not show any significant differences among groups before and after experiment. But urinary Ca/creatinine ration decreased signifi-cantly in Ca group after experiment(P<0.05) 3) Serum Ca and P levels did not show any significant differences among groups before and after experiment. But serum Ca level in creased significantly in Ca group after experiment(P<0.05) 3) Serum Ca and P levels did not show any significant differences among groups before and after experiment. But serum Ca level increased significantly in Ca group after experiment (P<0.05). 4) Serum PTH level also did not show any significant differences among groups before and after experiment. But serum calcitonin level decreased significantly in Ca group after experiment(P<0.05). The above results showed that it will be difficult to prevent degenerative bone loss without regular exercise and/or Ca supplementation in postmenopausal women having Korean usual diets.

• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.323-329
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• 1997

Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p<0.05), respectively$(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$. But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$. From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.

• Journal of Nutrition and Health
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• v.37 no.6
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• pp.423-430
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• 2004

This study was performed to evaluate the effect of red-yeast-rice on bone metabolism in overiectomized (OVX) rats. Forty female Sprague-Dawley rats (body weight 210 $\pm$ 5 g, 9 weeks old age) were divided into two groups. One group were OVX, and the other group received sham operation (SHAM), and received either control diet (20％ casein) or a red-yeast-rice power supplemented diet (0.1％) for 9 weeks. And then each rat group was further divided into control diet (casein 20％) and red-yeast-rice powder supplemented (0.1％) diet group. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur on 5, 9 weeks after feeding. The serum and urine concentrations of Ca and P were determined. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. And bone resorption rate was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Serum osteocalcin, growth hormone, IGF-l and calcitonin were analyzed using radioimmunoassay kits. Urinary Ca and P excretion were not significantly different among the groups. Within the OVX group, the red-yeast-rice group had a lower crosslinks value than the casein group. Therefore the red-yeast-rice supplemented groups had a lower bone resorption ratio than the casein group in the ovariectomized rats. And, the red-yeast-rice group had significantly higher IGF-l hormone than casein group in ovariectomized rats. The red-yeast-rice group had higher spine bone mineral content than those of control group within the OVX groups. This study was an important first step in establishing that the observed beneficial effects of red-yeast-rice on bone, and this study also established the need for a study on the long-term effect of this supplement in a human.

• Journal of Nutrition and Health
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• v.29 no.9
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• pp.950-957
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• 1996

This study was designed to investigate the effects of caffeine intake on Ca and P metabolism in ovariectomized rats. For this purpose, the ovariectomized female rats weighing 230.8$\pm$3.5g were divided into four groups, eight rats each ; control, low caffeine(LC), medium caffeine(MC)and high caffeine(HC) groups. They were supplied for six weeks with the caffeine of 0mg, 66.8mg, 167mg and 334mg per kilogram of diet, respectively, and the results are summarized as follows. 1) There were no significant differences in feed intake, feed efficiency ratio and body weight change among all of experimental groups. But liver weight(both total weight and weight/body weight) was significantly decreased by caffeine in MC group. 2) The weight of tibia was decreased by caffeine intake in MC and HC groups. But the length, Ca and P content of tibia and femur was not changed in all of caffeine groups. 3) Ca, PTH and calcitonin levels in serum were not affected by caffeine. While, serum P level in HC group was significantly increased as compared with the control. 4) The fecal excretion of Ca and P tended to be higher in the caffeine groups, and as the result, the absorption rate, retention and retention rate of Ca and P tended to be decreased. It was noteworthy that P retention was significantly lowered in HC group as compared with LC group. The results showed that, when caffeine was taken by ovarietomized rats, the weight of tibia was decreased and the retention rate of Ca and P tended to be lowered. Therefore, too much intake of caffeine for women whose bone mineral density of tibia is decreased after postmenopause seems to accelerate the decrease of bone mineral density due to the negative effect on metabolism of Ca and P.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.573-580
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• 1998

The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

• Korean Journal of Veterinary Research
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• v.38 no.2
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• pp.246-257
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• 1998

Endocrine cells in the thymus of duck(Anas platyrhynchos platyrhyncos, Linne) were studied immunohistochemically from 23 days of incubation to 32 weeks of age. Somatostatin-, growth hormone(GH)-, gastrin/cholecystokinin(Gas/CCK)-, polypeptide YY(PYY)-, S-100 protein(S-100 P)-, dopamine-, serotonin(5-HT)-, and bovine chromogranin (BCG)-immunoreactive cells were detected in the duck thymus by the PAP techniques. These immunoreactive cells were observed in the medulla and in the juxtacortical medulla. No immunoreactivity of calcitonin and bovine pancreatic polypeptide(BPP) antiserum were observed. The argyrophil cells by Grimelius techniques were observed from 23 days of incubation to 32 weeks of age and peaked in 5 weeks of age. In the early develpmental stage, the argyrophil cells were distributed only in the medulla, while these cells were distributed mainly in the medulla and a few cells were distributed in the corticomedullary junction from 3 weeks of age. These immunoreactive cells were generally round, oval and elliptical and occasionally spindle, polygonal and polymorphous with the long cytopslasmic processes in shape. The present study suggests that the intrathymic endocrine cells may associate with the functional maturation of T-lymphocytes on the establishment of immunity. The further study will be needed to elucidate the function of these thymic endocrine cells.

• Journal of the East Asian Society of Dietary Life
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• v.15 no.3
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• pp.264-270
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• 2005

This study was performed to evaluate the effect of red-yeast-rice on blood lipids and also to investigated the relation of blood lipids, bone related hormones, and bone mineral density in overiectomized rats. Forty female rats (body weight $210\pm5$g) were divided into two groups. The rats in the first group were ovariectomized which the others received sham operation (SHAM). And then each rat group was further divided into control diet $(casein\;20\%)$ and red-yeast-rice powder supplemented $(0.1\%)$ diet group. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus in spine and femur. Bone formation and bone resorption were measured by serum osteocalcin and urinary deoxypyridinoline (DPD) crosslinks value. Serum growth hormone, IGF-1 and calcitonin were analyzed using radioimmunoassay kits. The red-yeast-rice group had significantly lower the blood triglyceride concentration and had lower the blood total cholesterol concentration than casein group did in ovariectomized rats. And the red-yeast-rice group than casein group in ovariectomized rats. The red-yeast-rice group had significantly lower the atherogenic index than control group within the ovariectomized groups. In the experimental rats, serum total cholesterol concentration was negatively correlated with femur BMC and crosslink value. Crosslink value was negatively correlated with spine BMC and IGF-1. Osteocalcin concentration was negatively correlated with crosslink value. Growth hormone was negatively correlated with crosslink value and positively correlated with spine BMC. The findings of this study suggest that red-yeast-rices are beneficial for blood lipid in ovariectomized rats. And when considering a population-based public health approach to lowering cholesterol and bone loss, and preventing coronary heart disease and osteoporosis, the red-yeast-rice dietary supplement could provide a new approach for the maintenance of healthier cholesterol and bone.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.497-505
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• 2012

To determine the effects of Banggihwanggi-tang(BGHGT) on obesity, the obesity-related factors[gastrin, calcitonin gene related peptide(CGRP), serotonin, ghrelin, obestatin, glucagon-like peptide-1(GLP-1), insulin, orexin, leptin] were investigated in the stomach, pancreas, brain of mice by immunohistochemical(IHC) methods for 4 weeks. The change of body weight was more reduced in BGHGT administered group than that of control group. The IHC density of the gastrin and CGRP positive cells on pylorus was higher in BGHGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach was lower in BGHGT administered group than that of control group. The IHC of GLP-1 positive cells did not observe in the stomach of BGHGT administered groups. The IHC density of GLP-1 in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of insulin positive cells in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of orexin positive neurons in the diencephalon was slightly higher in BGHGT administered group than that of control group. The IHC density of NPY and leptin positive neurons was slightly higher in BGHGT administered group than that of control group. The IHC density of serotonin positive neurons was higher in BGHGT administered group than that of control group. Therefore, we conclude that BGHGT activates appetite inhibitor through appetite related enteroendocrine cells and neuropeptides in stomach, pancreas and brain, and this activation may also be responsible for the inhibition of feeding behavior.

• Biomedical Science Letters
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• v.11 no.3
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• pp.365-373
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• 2005

The aim of this study was to investigate the alterations in meningeal blood flow by stimulation of trigeminovascular system. An open cranial window was prepared on the right parietal bone of male Sprague-Dawley rats. Trigeminovascular system was stimulated by electrical stimulation of trigeminal ganglion (ETS), somatosensory (whisker) stimulation, or topical applications of capsaicin and neuropeptides including substance P and calcitonin gene-related peptide (CGRP). Neonatal capsaicin pretreatment was performed with subcutaneous administration of capsaicin (50 mg/kg) within the first 24 hours after birth. Changes in regional blood flow of dural artery (rDBF) and pial artery (rPBF) were continuously measured through the cranial window by laser-Doppler flowmetry. Both ETS and capsaicin caused a chain of alterations in rPBF and rDBF responses, i.e., an immediate transient decrease followed by rapid and marked increase in rPBF, which were significantly attenuated not only by pretreatments with L-733,060, a $NK_1$ receptor blocker, $CGRP_{8-37}$, a $CGRP_1$ receptor blocker, and 7-nitroindazole monosodium salt (7-NINA), a neuronal nitric oxide synthase inhibitor but also by neonatal capsaicin treatment. Exogenous neuropeptides including substance P and CGRP increased the meningeal blood flow, which was significantly attenuated not only by pretreatment with L-733,060 and $CGRP_{8-37}$, respectively, but also by pretreatment with 7-NINA. The rPBF response to whisker stimulation was significantly attenuated not only by trigeminovascular system injuries including nasociliary nerve denervation and neonatal capsaicin treatment but also by pretreatments with L-733,060, $CGRP_{8-37}$ and 7-NINA. These results suggest that the stimulation of trigeminovascular system causes prominent alterations in meningeal blood flow, and that neuropeptides as well as nitric oxide in the trigeminovascular system are importantly implicated in the regulation of meningeal blood flow.